Effect of Jiawei Tongqiao Huoxue decoction in basilar artery dolichoectasia mice through yes-associated protein/transcriptional co-activator with PDZ-binding motif pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Jiawei Tongqiao Huoxue decoction (JTHD), composed of Acorus calamus var. angustatus Besser, Paeonia lactiflora Pall., Conioselinum anthriscoides 'Chuanxiong', Prunus persica (L.) Batsch, Ziziphus jujuba Mill., Carthamus tinctorius L., Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep, Zingiber officinale Roscoe, Leiurus quinquestriatus, and Moschus berezovskii Flerov, was developed based on Tongqiao Huoxue decoction in Wang Qingren's "Yilin Gaicuo" in the Qing Dynasty. It has the effect of improving not only the blood flow velocity of vertebral and basilar arteries but also the blood flow parameters and wall shear stress. Especially in recent years, the potential efficacy of traditional Chinese medicine (TCM) for the treatment of basilar artery dolichoectasia (BAD) has attracted great attention as there are still no specific remedies for this disease. However, its molecular mechanism has not been elucidated. To identify the potential mechanisms of JTHD will help to intervene BAD and provide a reference for its clinical application. AIM OF THE STUDY: This study aims to establish a mouse model of BAD and explore the mechanism of JTHD regulating yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) pathway for attenuating BAD mice development. MATERIALS AND METHODS: Sixty post-modeling C57/BL6 female mice were randomly divided into sham-operated, model, atorvastatin calcium tablet, low-dose JTHD, and high-dose JTHD groups. After 14 days of modeling, the pharmacological intervention was given for 2 months. Then, JTHD was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). ELISA was utilized to detect the changes in vascular endothelial growth factor (VEGF) and lipoprotein a (Lp-a) in serum. EVG staining was conducted to observe the pathological changes of blood vessels. TUNEL method was employed to detect the apoptosis rate of vascular smooth muscle cells (VSMCs). Micro-CT and ImagePro Plus software were used to observe and calculate the tortuosity index, lengthening index, percentage increase in vessel diameter, and tortuosity of the basilar artery vessels in mice. Western blot analysis was performed to detect the expression levels of YAP and TAZ proteins in the vascular tissues of mice. RESULTS: Many effective compounds such as choline, tryptophan, and leucine with anti-inflammation and vascular remodeling were identified in the Chinese medicine formula by LC-MS analysis. The serum levels of VEGF in the model mice decreased significantly while the levels of Lp-a increased obviously compared with those in the sham-operated group. The intima-media of the basilar artery wall showed severe disruption of the internal elastic layer, atrophy of the muscular layer, and hyaline changes of the connective tissue. Apoptosis of VSMCs added. Dilatation, elongation, and tortuosity of the basilar artery became notable, and tortuosity index, lengthening index, percentage increase in vessel diameter, and bending angle remarkably improved. The expression levels of YAP and TAZ protein in blood vessels elevated conspicuously (P < 0.05, P < 0.01). JTHD group markedly reduced the lengthening, bending angle, percentage increase in vessel diameter, and tortuosity index of basilar artery compared with the model group after 2 months of pharmacological intervention. The group also decreased the secretion of Lp-a and increased the content of VEGF. It inhibited the destruction of the internal elastic layer, muscular atrophy, and hyaline degeneration of connective tissue in basilar artery wall. The apoptosis of VSMCs was decreased, and the expression levels of YAP and TAZ proteins were abated (P < 0.05, P < 0.01). CONCLUSIONS: The mechanism of inhibition of basilar artery elongation, dilation, and tortuosity by JTHD, which has various anti-BAD effective compound components, may be related to the reduction in VSMCs apoptosis and downregulation of YAP/TAZ pathway expression.

Vertebral artery dominance, brainstem auditory evoked potential, and vertigo of vascular origin.

OBJECTIVE: Vertebral artery dominance (VAD) is defined when there is a significant difference between the diameters of the vertebral arteries (VAs). VAD may be a risk factor for vertigo of vascular origin. The objectives of this study were: (1) to investigate changes of brainstem auditory evoked potential (BAEP) in patients with vertigo caused by VAD through magnetic resonance; and (2) to understand the possible mechanism(s) by which VAD triggers vertigo of vascular origin. METHODS: This prospective study involved 64 patients with vertigo, including 35 patients with VAD (VAD group) and 29 without VAD (non-VAD group) as detected by head magnetic resonance angiography. Age, sex, and other clinical histories were comparable in both groups. The degree of vertigo was graded and BAEP examination was performed in each patient. BAEP changes as well as their correlations of BAEP with the dominant VA and basilar artery (BA) were analyzed in both groups. RESULTS: The rate of abnormal BA shapes was 60% in the VAD group compared with 34.5% in the non-VAD group (Chi-square = 4.135, P<0.05). The median BA curvature was higher in the VAD group than that in the non-VAD group, 3.67 and 1.73 mm, respectively (P<0.01). Peak latencies (I, III, and V) in the VAD group were longer than those in the non-VAD group (P<0.01), but the difference in the III did not reach statistical significance (t = 1.916, P>0.05). Interpeak latencies (III-V and I-V) were longer in the VAD group than those in the non-VAD group (P<0.05); there was no significant difference in the interpeak latencies of I-III (P>0.05). The III-V/I-III ratios were higher in the VAD group than those in the non-VAD group. The vertigo severity level was significantly higher in the VAD group than that in the non-VAD group (3.2 ± 1.0 versus 2.2 ± 0.7). The vertigo severity level correlated with VAD and every major anomaly index of BAEP; its correlations with III-V/I-III were remarkably significant (r = 0.617, P = 0.013). CONCLUSION: The incidence of abnormal BA shapes and abnormal BAEP, and the vertigo severity level were higher in VAD patients. Moreover, VAD was found to correlate with abnormal BAEP, suggesting that VAD contributed to vertigo of vascular origin.